Methionine enkephalin as a possible neuromodulator of regional cerebral blood flow

In swine, cerebral blood flow was documented by a left ventricular injection of radiolabeled 15-micron spheres. Utilizing this procedure, the effect of the putative neurotransmitter methionine-enkephalin on regional cerebral blood flow was systemically evaluated. Our results revealed that a peripheral infusion of methionine enkephalin into miniature swine significantly increased cerebral blood flow in the basal ganglia, cerebellum, pons, inferior parietal cortex and frontal cortex. Non-significant increases were observed in the hippocampus, occipital cortex and medulla oblongata while no effect on blood flow was observed in the pituitary gland. Significance of these results in the potential role of methionine enkephalin as a modulator of blood flow to the brain.     

The effects of acute and chronic morphine on regional distribution of cardiac output in brain

Both acute and chronic administration of morphine resulted in an increase in the percent cardiac output received by brain. However, various brain regions were affected differently by the drug treatments. The greatest increases in percent cardiac output received after chronic administration of morphine occurred in pons and cerebellum, while the greatest increases after acute administration occurred in cortex and midbrain. The changes found are in contrast with earlier studies which suggest that morphine has no effect on cerebral blood flow.     

The effects of acute and chronic morphine on regional distribution of cardiac output in brain

Summary Both acute and chronic administration of morphine resulted in an increase in the percent cardiac output received by brain. However, various brain regions were affected differently by the drug treatments. The greatest increases in percent cardiac output received after chronic administration of morphine occurred in pons and cerebellum, while the greatest increases after acute administration occurred in cortex and midbrain. The changes found are in contrast with earlier studies which suggest that morphine has no effect on cerebral blood flow.     

An ultrastructural investigation of the effects of perinatal malnutrition on E-PTA-stained synaptic junctions.

The effect of protein-deficient diet on E-PTA stained synapses in rat cerebral cortex was studied by electron microscopy. No significant difference was observed in synaptic morphology between control and malnourished animals at 35 days postnatal.     

Cerebral ammonia production during hypoglycemia in the newborn calf.

The effect of insulin hypoglycaemia on cerebral blood flow, and cerebral metabolic rates of glucose, oxygen and ammonia was investigated in the unanaesthetized newborn calf. A net loss of ammonia from the brain occurred during hypoglycaemia, and was greater in convulsing than in comatose animals.     

Methionine enkephalin inhibits the bursting activity of the Br-type neuron in Helix pomatia L

The present study demonstrates that methionine enkephalin can inhibit the normal bursting activity pattern of the RPal or Br-type neuron and this inhibition can be blocked by prior treatment with naloxone, the selective opiate antagonist. The study demonstrates indirectly the presence of opiate-like receptors in Helix pomatia.     

Demonstration of vascular redistribution after carotid clamping in rats

Summary in Long Evans rats, the vertebral arteries supply only the brain stem. Simultaneous application of clamps to both carotid arteries results in a considerable fall of cerebral blood flow and eventually death. If an interval of about 4 days is allowed between the clamping of the 2 carotids, redistribution of blood flow takes place. Owing to this mechanism, 50% of the rats survive with a satisfactory restoration of cerebral blood flow.     

Dopamine and cerebral cortical blood flow in the rat

Summary Dopamine topically applied to the cerebral cortex (1–20 g/ml) or administered i.v. (0.5–64 g/kg/min) has no effects on cerebral cortical blood flow in the rat.     

Increase in the oxygen available to the cerebral cortex after the administration of carbonic anhydrase inhibitors]

Oxygen tension (pO2) in cerebral cortex was measured by polarographic method in unanesthetized rabbits. Intravenous administration (25 mg/kg) of carbonic anhydrase inhibitors (acetazolamide, methazolamide, dichlorphenamide, sulthiame) induced an early important rise of cortical p O2, which is not dependent on increase of p O2 and p CO2 and decrease of pH in arterial blood. High dosage of acetazolamide (250 mg/kg) produced the same effect and did not suppress the increase of cortical p O2 under air-CO2 inhalation. This result suggests that CO2 might act specifically upon cerebral vessels.     

DNA fragmentation in leukocytes following repeated low dose sarin exposure in guinea pigs

The objective of this study was to determine levels of DNA fragmentation in blood leukocytes and parietal cortex from guinea pigs following repeated lowlevel exposure to the chemical warfare nerve agent (CWNA) sarin. Guinea pigs were injected (s.c.) once a day for 10 days with saline, or 0.1, 0.2, or 0.4 LD₅₀ (50% mean lethal dose) sarin dissolved in sterile physiological saline. Blood and parietal cortex was collected after injection at 0, 3, and 17 days recovery and evaluated for DNA fragmentation using single-cell gel electrophoresis (Comet assay). Cells were imaged using comet analysis software and three parameters of DNA fragmentation measured: tail length, percent DNA in the tail, and tail moment arm. Repeated low-dose exposure to sarin produced a dose-dependent response in leukocytes at 0 and 3 days post-exposure. There was a significant increase in all measures of DNA fragmentation at 0.2 and 0.4 LD₅₀, but not at 0.1 LD₅₀. There was no significant increase in DNA fragmentation in any of the groups at 17 days post-exposure. Sarin did not produce a systematic dose-dependent response in parietal cortex at any of the time points. However, significant increases in DNA fragmentation at 0.1 and 0.4 LD₅₀ were observed at 0 and 3 days post-exposure. All measures of DNA fragmentation in both leukocytes and neurons returned to control levels by 17 days post-exposure, indicating a small and non-persistent increase in DNA fragmentation following repeated low-level exposure to sarin. Received 23 July 2007; received after revision 23 August 2007; accepted 3 September 2007 Research was conducted in compliance with the Animal Welfare Act, and other Federal statutes and regulation relating to animals and experiments involving animals and adheres to the principles stated in the Guide for the Care and Use of Laboratory Animals, NIH publication 85-23. The views of the authors do not purport to reflect the position of the Department of the Army or the Department of Defense (para 4-3), AR 360–365.     

Cerebral ammonia production during hypoglycaemia in the newborn calf

Summary The effect of insulin hypoglycaemia on cerebral blood flow, and cerebral metabolic rates of glucose, oxygen and ammonia was investigated in the unanaesthetized newborn calf. A net loss of ammonia from the brain occurred during hypoglycaemia, and was greater in convulsing than in comatose animals.Acknowledgments. The expert assistance of Mr P.M.M. Bircham and Miss B.N. O'Connor is gratefully acknowledged. This work was supported by the Medical Research Council.     

May K+ ions stimulate the formation of cyclic AMP in the brain independently on their depolarizing action?

Summary The effect of potassium ions on the formation of adenosine 3,5-monophosphate (cAMP) in the rat cerebral cortex in vivo was studied under conditions where development of spreading depression had been blocked by pretreatment of the cerebral cortex by topically applied magnesium ions. A linear relationship between potassium concentrations applied to the cortical surface and levels of cAMP has been found. Moreover, potentiation of the K⁺-effect by magnesium ions has been observed.     

Potassium transfer from brain to blood during sustained hyponatraemia in the newborn calf

Summary The effect of dilutional hyponatraemia on cerebral blood flow and oxygen consumption, and net transfer of K⁺ to the circulation from brain tissue drained by the sagittal sinus was investigated in anaesthetized calves. Cerebral blood flow decreased, and net transfer of K⁺ to the circulation increased during hyponatraemia.Acknowledgments. The expert assistance of Miss B.N. O'Connor, Miss D. McNaughton and Mr P.M.M. Bircham is gratefully acknowledged.     

Proposed effects of brain noradrenaline on neuronal activity and cerebral blood flow during REM sleep.

We propose that the observed increases of both neuronal activity and cerebral blood flow seen throughout the brain during REM sleep may be effects of decreased central noradrenaline release.     

Proposed effects of brain noradrenaline on neuronal activity and cerebral blood flow during REM sleep

Summary We propose that the observed increases of both neuronal activity and cerebral blood flow seen throughout the brain during REM sleep may be effects of decreased central noradrenaline release.     

Methionine enkephalin inhibits the bursting activity of the Br-type neuron inHelix pomatia L.

Summary The present study demonstrates that methionine enkephalin can inhibit the normal bursting activity pattern of the RPal or Br-type neuron and this inhibition can be blocked by prior treatment with naloxone, the selective opiate antagonist. The study demonstrates indirectly the presence of opiate-like receptors inHelix pomatia.Acknowledgments. This work was funded by grant RR 08171 Division of Research Resources and NIMH, and a National Academy of Sciences Travel grant and a Hungarian Academy of Sciences research support award to G.B.S. We also gratefully acknowledge thoughtful comments from Dr J. Salanki.     

D-ala2-Metenkephalinamide blocks the synaptically elicited cortical spreading depression in rats

Spreading depression (SD) was elicited in rats anesthetized with pentobarbital by a train of 8 electrical pulses (0.1 ms, 10 Hz) applied to parietal cortex. Local application of 50 micrograms of D-ala2-metenkephalinamide (DAME) on the stimulated area evoked one or two SD waves followed by an increase of SD threshold from 40 V to 90 V. This effect could be partly prevented by naloxone (1 mg/kg i.p.) and reversed by local application of 4-aminopyridine (10(-3) M, 2 microliters), which reduced SD threshold to 5 and 20 V in normal and DAME-treated cortex, respectively. It is argued that DAME exerts an inhibitory effect on cortical neurons and that the initial SD facilitation is due to initial blockade of inhibitory neurons in the superficial cortical layers.     

Correlation between brain blood flow and catecholamine levels in rat brain areas under hypobaric hypoxia

Summary Hypobaric hypoxia induces an important increase in the cerebral blood flow in all areas and more particularly in the bulb and hypothalamus; the increase in the cerebral blood flow allows for an oxygen intake sufficient to maintain the norepinephrine level in these structures.     

Nonsympathetic dilator innervation of cat cerebral arteries.

The results presented provide strong support for the presence of vasodilator innervation in the cat cerebral arteries. The dilator innervation is neither adrenergic nor cholinergic and does not originate in the superior cervical ganglia. The nature of the vasodilator transmitter is unidentified. Such innervation, however, may be involved in the regulation of cerebral blood flow, especially in view of the capability of some cat cerebral vessels to develop intrinsic muscle tone.     

Neuroprotective effects of <Emphasis Type="Italic">Ginkgo biloba</Emphasis> extract

Ginkgo biloba extract has been therapeutically used for several decades to increase peripheral and cerebral blood flow as well as for the treatment of dementia. The extract contains multiple compounds such as flavonoids and terpenoids that are thought to contribute to its neuroprotective and vasotropic effects. In this review, we summarize the experimental results on the mechanism of neuroprotection induced by standardized extract of Ginkgo biloba leaves (EGb 761) and its constituents. The effects described mostly in animals include those on cerebral blood flow, neurotransmitter systems, cellular redox state and nitric oxide level. Furthermore, we discuss the current status of clinical trials as well as undesired side effects of EGb 761.Received 21 November 2002; received after revision 8 March 2003; accepted 17 March 2003